The proposed research will compare behavior, functional brain responses, and anatomical connectivity in the mirror system in macaques, chimpanzees, and humans. The mirror system is thought to underlie action understanding by allowing individuals to simulate others'actions as if they were performing them. However, several unresolved issues limit the extent to which the mirror system can be linked to human social cognition. First, macaque mirror system results are largely replicated. Second, the equivalence between macaque and human results is unclear because they involve different methodologies. Third, macaque and human mirror system responses differ, with only the human mirror system responding to actions that do not involve objects. Fourth, macaques lack some behaviors which have been linked to the mirror system in humans, most notably imitation. This proposal will address the first two issues by validating basic macaque mirror system findings using a methodology comparable to those used in humans. It will address the second two issues by directly investigating how mirror system responses and connectivity differ among primate species. The main hypothesis is that an evolved broadening in mirror system response properties, via increased connectivity with other brain networks, allowed these cells to respond to, and thus simulate, a wider variety of observed stimuli. This hypothesis will be tested using a combination of behavioral tasks, in vivo functional neuroimaging, and structural diffusion tensor imaging. Aim 1 will employ 18F-FDG positron emission tomography to compare the neural correlates of the execution and observation of actions with and without objects in macaques and chimpanzees. Aim 1 will also procure behavioral indices of imitation ability in each subject. Aim 2 will use diffusion tensor imaging to compare white matter pathways linking the components of the mirror system in macaques, chimpanzees, and humans. The behavioral and functional brain responses obtained in Aim 1 will be compared to the anatomical results obtained in Aim 2. In this way, species and individual differences in imitation ability can be linked to differences in brain responses and anatomical connectivity. PUBLIC HEALTH RELEVANCE: Disorders like autism and schizophrenia affect social skills like the ability to link perceived facial expressions to internal emotional states and the ability to infer goals and intentions from observed actions. These disorders appear to be uniquely human, and the abilities they affect are developed in humans to an extent not seen in other primates. Because these abilities reflect a recent evolutionary change in function, identification of the underlying evolutionary changes in anatomy can locate potential foci for these diseases.